title: Comparative genetics of a highly divergent DRB microsatellite in different macaque species.
abstract: The DRB region of the major histocompatibility complex (MHC) of cynomolgus and rhesus macaques is highly plastic, and extensive copy number variation together with allelic polymorphism makes it a challenging enterprise to design a typing protocol. All intact DRB genes in cynomolgus monkeys (Mafa) appear to possess a compound microsatellite, DRB-STR, in intron 2, which displays extensive length polymorphism. Therefore, this STR was studied in a large panel of animals, comprising pedigreed families as well. Sequencing analysis resulted in the detection of 60 Mafa-DRB exon 2 sequences that were unambiguously linked to the corresponding microsatellite. Its length is often allele specific and follows Mendelian segregation. In cynomolgus and rhesus macaques, the nucleotide composition of the DRB-STR is in concordance with the phylogeny of exon 2 sequences. As in humans and rhesus monkeys, this protocol detects specific combinations of different DRB-STR lengths that are unique for each haplotype. In the present panel, 22 Mafa-DRB region configurations could be defined, which exceeds the number detected in a comparable cohort of Indian rhesus macaques. The results suggest that, in cynomolgus monkeys, even more frequently than in rhesus macaques, new haplotypes are generated by recombination-like events. Although both macaque species are known to share several identical DRB exon 2 sequences, the lengths of the corresponding microsatellites often differ. Thus, this method allows not only fast and accurate DRB haplotyping but may also permit discrimination between highly related macaque species.
authors.affiliation: Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, The Netherlands. nanine.de.groot@bprc.nl
authors.forename: Nanine
authors.initials: N
authors.lastname: de Groot
authors.forename: Gaby G M
authors.initials: GG
authors.lastname: Doxiadis
authors.forename: Annemiek J M
authors.initials: AJ
authors.lastname: de Vos-Rouweler
authors.forename: Natasja G
authors.initials: NG
authors.lastname: de Groot
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Bontrop
mesh_terms: D000818:Animals; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D005091:Exons / Q000235:genetics; D005802:Genes, MHC Class II; D008252:Macaca fascicularis / Q000235:genetics*; D008253:Macaca mulatta / Q000235:genetics*; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012335:RNA, Ribosomal / Q000235:genetics; D011995:Recombination, Genetic; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
chemical_list: D004272:DNA, Mitochondrial; D004275:DNA, Ribosomal; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S